Drug delivery

ABSTRACT

A method and apparatus of treating tissue adjacent a bodily conduit using thermotherapy, while preventing obstructions of the bodily conduit due to edema, includes injection of a drug-encapsulated within a heat-sensitive carrier, such as a liposome, within a region of tissue to be treated. The heat produced by the energy-emitting source heats a portion of the tissue surrounding the bodily conduit to a temperature of approximately 43° C. for a time sufficient to destroy the heated portion of the tissue. In addition, the heat produced by the energy-emitting source activates the heat-sensitive carrier to activate the release of the encapsulated drug and the drug targets the tissue to be heated. The focused energy of the energy-emitting source together with the compression acting on the target area can assist in delivering drugs to the target area so that a natural stent has a long term efficacy.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. Ser. No. 10/504,302, filedMay 13, 2005, now U.S. Pat. No. 7,833,220 which is related to U.S. Ser.No. 09/954,194, filed Sep. 18, 2001, now U.S. Pat. No. 6,958,075, andwhich claims priority to PCT Application No. PCT/US02/29048, filed Sep.13, 2002, and also to U.S. Ser. No. 60/356,750, filed Feb. 15, 2002, andwhich also is a national stage application of PCT Application No.PCT/US03/04512, filed Feb. 19, 2003. The entirety of each of these isincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention generally relates to a system and method foradministering focused energy to a body using either a single energyapplicator or multiple microwave applicators, warmed fluid andcompression in order to treat visible tumors and microscopic malignantand benign cells in tissue with thermotherapy. In particular, thepresent invention relates to a transurethral catheter for microwavethermal and warming therapy with compression of prostate tissue adjacenta urethra to create a biological stent.

2. Description of the Prior Art

In order to treat the prostate with thermotherapy, it is necessary toheat a significant portion of the prostate gland while sparing healthytissues in the prostate as well as the surrounding tissues including theurethral and rectal walls of a patient. The prostate gland encircles theurethra immediately below the bladder. The prostate, which is the mostfrequently diseased of all internal organs, is the site of a commonaffliction among older men, benign prostatic hyperplasia (BPH), acuteprostatitis, as well as a more serious affliction, cancer. BPH is anonmalignant, bilateral nodular tumorous expansion of prostate tissueoccurring mainly in the transition zone of the prostate. Left untreated,BPH causes obstruction of the urethra that usually results in increasedurinary frequency, urgency, incontinence, nocturia and slow orinterrupted urinary stream.

Recent treatment of BPH includes transurethral microwave thermotherapyin which microwave energy is employed to elevate the temperature oftissue surrounding the prostatic urethra above about 45° C., therebythermally damaging the tumorous prostate tissue. U.S. Pat. Nos.5,330,518 and 5,843,144 describe methods of ablating prostate tumoroustissue by transurethral thermotherapy, the subject matter of which isincorporated by reference. However, improvements still need to be madein this type of therapy to further maintain or enhance the patency ofthe urethra after the thermotherapy treatment. In particular, urine flowis not always improved despite ablation of the tumorous tissue causingconstriction of the urethra because edema produced by the transurethralthermo-therapy treatment blocks the urethra passage resulting inpatients treated by the above methods to be fitted with catheters forseveral days or weeks after the thermotherapy treatment.

U.S. Pat. Nos. 5,007,437, 5,496,271 and 6,123,083 disclose transurethralcatheters with a cooling balloon in addition to the anchoring or Foleyballoon and are incorporated by reference herein. However, these patentscirculate fluid, which acts as a coolant for removing heatpreferentially from the non-prostatic tissue adjacent thereto, throughthe cooling balloons. The '083 patent further discloses the use of athermotherapy catheter system taught by U.S. Pat. No. 5,413,588 thatemploys chilled water between about 12°-15° C. as the coolant. Chilledwater significantly cools the urethra adjacent the cooling balloon.Likewise, the '271 patent describes a coolant as the fluid to keep theurethral wall temperatures cool. This chilling of the urethra does notaid in maintaining an opening within the heated urethra after thecooling balloon is removed, and reduces the therapeutic effect in thetissue immediately adjacent the urethral wall.

Another known alternative to thermal surgery, as described in U.S. Pat.No. 5,499,994, is to insert a dilation balloon in the urethra and toexpand the dilation balloon to compress the obstructed urethra. However,the expansion of the dilation balloon occurs over 24 hours and thepatient still is not cured of the diseased prostate and can causeadverse effects (e.g., tearing of the urethral walls). U.S. Pat. No.6,102,929 describes a post-operative procedure where the prostate tissueis expanded after the surgical procedure to enlarge the urethra toenable a patient to void comfortably. This expansion requires insertionof another device and requires the device to remain in the patient for aday or more.

In view of the fact that post-treatment catheters or other devices arestill considered necessary by the medical community, furtherimprovements are needed in thermotherapy to avoid the obstruction causedby edema and to maintain and enhance the opening of the urethra.

SUMMARY OF THE INVENTION

The present invention is directed to a device and a method for thermallytreating tissue adjacent a bodily conduit, such as a urethra, whilepreventing obstructions of the bodily conduit due to edema. To achievethis object, the instant invention employs a catheter with anenergy-emitting source and a compression balloon surrounding theenergy-emitting source through which a warmed fluid flows to warm thebodily conduit walls adjacent the compression balloon.

While the instant invention will be described with respect to apreferred embodiment where the bodily conduit is the urethra andprostatic tissue is to be treated by thermotherapy, the combination ofwarmed fluid, compression and microwaves can be used to achieve theabove goal in other bodily conduits including, but not limited to,cardiovascular, esophageal, nasal pharynx, and rectal cavities. That is,it is a goal of the instant invention to open up bodily conduits so thatthe normal function of that conduit is not hampered. The power to theenergy-emitting source and diameters and shaping of the compressionballoon and catheter will vary depending upon the tissue or bodilyconduit to be treated.

A minimally invasive RF, microwave, or ultrasound focused-energyproducing system that compresses the targeted area is used incombination with heat-sensitive liposomes encapsulating pharmaceuticalagents, for minimally invasive targeted treatment of large tumor masses,as well as the treatment of non-cancerous enlarged prostate. The focusedenergy heats the targeted area and activates the heat-sensitiveliposomes and releases drugs in targeted tissue in accordance with theinvention.

Unlike known techniques that circulate a coolant to cool the urethralwalls, the instant invention circulates a warmed fluid to maintain thetemperature of the urethra above 30° C. Applicants recognized that abiological stent or molded opening was not able to be formed with cooledcirculation fluid (i.e., fluid circulated into a patient in the range of25° C.-30° C.). A preferred range of temperature for the warmed fluidwould be between 30° to 60° C. A preferred example would be to circulatefluid into a patient at 35° C. Applicants have formed a biological stentwhen the external temperature of the warmed fluid before circulationthrough a patient measures 33° C.

According to the invention, a select volume of collagen-containingtissue surrounding the urethra is heated to a temperature greater thanabout 43° C. for time sufficient to substantially destroy the selectvolume of tissue. Prior to energizing the energy-emitting source, thepreshaped compression balloon is filled with the warmed fluid to expandthe urethral walls compressing the prostate thereby reducing blood flowin the prostate surrounding the urethral walls so that theenergy-absorptive heating is more efficient in the region of constrictedblood supply. As a result, the proteins of the urethral walls becomedenatured or are unraveled in the presence of the heat emitted from theenergy-emitting source. The warmed fluid, which expands the compressionballoon, supports the denaturing process while preventing the absorbed,energy-emitted heat from burning the urethral walls. This denaturingallows the urethral walls to conform to the expanded shape of theurethra created by the compression balloon and reduces the elasticity ofthe urethral walls so that a stent reinforcement period following theheating naturally solidifies the expanded shape resulting in abiological stent. That is, the expanded bodily conduit walls do notreturn to their previous shape after the compression balloon is deflatedand removed thereby achieving a natural opening in the a bodily conduit,such as a urethra.

According to a preferred embodiment of the invention, a stentreinforcement period of approximately 10 minutes or less follows theheating step. The stent reinforcement period maintains the pressure ofthe compression balloon after power to the energy-emitting source hasbeen turned off so that a solidified expanded urethra is achievedminutes after thermotherapy and a catheter or other device is notnecessary.

The compression balloon is generally cylindrical with a sloped area onboth sides of the compression balloon and is symmetrical along thelength of the diameter according to a preferred embodiment. The positionof the energy-emitting source in the preferred embodiment may be fixed.However, the compression balloon may be of any shape to create a desiredmold or stent within a bodily conduit or urethra and may be asymmetricalalong the length of the catheter.

The compression balloon needs to maintain about 10-25 psi against theurethral wall along the length of the catheter with the preferred levelof pressure being about 15 psi. The compression balloon may have avariable diameter along the length of the catheter. Alternatively, thecompression balloon may be a single balloon or multiple balloons.

In one embodiment, the diameter of the compression balloon varies acrossthe radius to achieve an asymmetric molding of the bodily conduit.Alternative shapes of the compression balloon would include cone-shapedcylinders where the apex is adjacent the bladder neck or directed awayfrom the bladder neck depending on the desired biological stent. Thesecone-shaped cylinders would enable the energy-emitted heat to focus on aparticular area surrounding the bodily conduit, as well as create abiological stent or opening corresponding to this shape.

According to the invention, a warmed fluid is preferably circulatedthrough the compression balloon in conjunction with an outflowrestriction so that the pressure of flow in the balloon is maintained atabout 10-25 psi. The positioning of the inlet and outlet orifices in thecompression balloon enables laminar flow within the compression balloon.Further, the inlet and outlet orifices in the compression balloon arearranged as to minimize air pockets in the balloon and thus, “hot spots”which occur as a result of the air pockets.

In addition to the various shapes of the compression balloon, thecompression balloon could be partially covered with a grounded orungrounded conductive material that shields or absorbs theenergy-emitting rays so that the heat could be reduced at some portionsof the prostatic tissue and focused at other portions. In thisembodiment, the energy-emitting source or microwave antenna may bemovable so that the position of its energy-emitting portion can vary tooptimize the heating of tissue for a particular therapy. The preferredlocation and movement, if any, of the energy-emitting source woulddepend on the size, shape and the shielding of the compression balloon.

In another embodiment, the focused radiation together with thecompression from the compression balloon may be used to activateheat-sensitive liposomes carrying a drug. Consequently, a thermodynamictherapy system including a thermally activated drug delivery system,which is provided within the bloodstream of a patient under therapy,efficiently transfers heat so that drug delivery within the prostate canbe improved. The drug delivery system releases a selected drug at thetreatment area in response to the treatment area being heated by thefocused radiation. A higher concentration of released pharmaceuticalagent carried in the heat-sensitive liposomes or other heat-sensitivedrug carrier can result in a long-term efficacy of the treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the invention will be furtherunderstood from the following detailed description of the preferredembodiment with reference to the accompanying drawings in which:

FIG. 1 is a vertical sectional view of a male pelvic region showingurinary organs affected by benign prostatic hyperplasia and an insertedcatheter according to the invention with inflated compression and Foleyballoons;

FIG. 2 is an enlarged portion of FIG. 1;

FIG. 3 is a plan view of the urethral catheter of the present invention;

FIG. 3 a is a cross-sectional view of the urethral catheter of FIG. 3taken along line a-a;

FIG. 3 b shows an alternative embodiment of the warmed fluid pumpingsystem;

FIG. 4 illustrates the fluid flow through the catheter for inflation ofthe compression balloon;

FIGS. 5 a and 5 b are schematic, cross-sectional views of a urethrashowing the compression balloon in the uninflated and inflated states,respectively to illustrate the expansion of the urethral walls andprostate according to the invention;

FIG. 6 is a schematic cross-sectional view of the urethra illustratingan inflated, asymmetric compression balloon according to the invention;and

FIGS. 7 a-d illustrate alternative compression balloon shapes andtechniques for additional shielding implementations.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is directed to a device and a method for thermallytreating tissue adjacent a bodily conduit, such as a urethra, whilepreventing obstructions of the bodily conduit due to edema. In additionto focused energy and compression, drug delivery may aid in long termefficacy of treatment. The following will describe method, systems andalternatives of the method and apparatus according to the presentinvention.

A first method and apparatus of maintaining or expanding the diameter ofthe urethra into a selected urethral shape after microwave thermotherapytreatment for benign prostatic hyperplasia to restore patency to theurethra is illustrated in FIGS. 1-6. FIG. 1 is a vertical sectional viewof a male pelvic region showing the effect of benign prostatichyperplasia (BPH) on the urinary organs. Urethra 10 is a duct leadingfrom bladder 11, through prostate 12 and out orifice 13 of penis end 14.Benign tumorous tissue growth within prostate 12 around urethra 10causes constriction of urethra 10, which interrupts the flow of urinefrom bladder 11 to orifice 13. The tumorous tissue of prostate 12, whichencroaches urethra 10 and causes the constriction (not shown, ascompression balloon 112 is inflated), can be effectively removed byheating and necrosing the encroaching tumorous tissue. Ideally, with thepresent invention, periurethral tumorous tissue of prostate 12 anteriorand lateral to urethra 10 is heated and necrosed while avoidingunnecessary and undesirous damage to urethra 10 and to adjacent healthytissues, such as external sphincter 17, rectum 18, and bladder neck 19.

FIG. 2 is an enlarged sectional view of FIG. 1 illustrating specificanatomical features including urethra 10 and bladder 11 and showing acatheter 100 according to the invention with an inflated compressionballoon 112 and an inflated Foley or anchoring balloon 118. As shown onFIGS. 1-4, the instant invention employs a catheter 100 with anenergy-emitting source 110 and a compression balloon 112 surrounding theenergy-emitting portion of source 110 through which a warmed fluid flowsto warm the urethra walls adjacent the compression balloon. A selectiveheating of benign tumorous tissue in prostate 12 (transurethralthermotherapy) is made possible by energy-emitting-containing catheter100 of the present invention. A rectal probe 102 with a number ofsensors is inserted into rectum 18 and measures the amount of heatgenerated by the absorbed emitted energy at the rectal wall.

As shown in FIG. 2, three sensors 104 are mounted on probe 102. Thesensors are preferably integrally mounted at differing radial locationson the probe and spaced approximately 1 centimeter from one another.Foley balloon 118 is inserted into a patient's bladder so that theproximal end of the compression balloon is located at the patient'sprostate immediately distal of the bladder neck. The length ofcompression balloon 112 varies depending upon the size of a patient'sbladder. A typical length of the compression balloon would be about 40millimeters and the length can range from 25 to 60 millimeters.

Catheter 100 would be around 18 French (French is a measurement equal to0.333 mm or 0.013 inch). Since the average diameter of a male adulthuman is about 22 French, the deflated compression balloon 112 thatsurrounds the catheter would add approximately 2 French so that diameterof catheter 100 and balloon 112 would be less than that of the patient'surethra for ease of insertion and less pain for the patient. Multi-LumenShaft 100 and associated molded parts are preferably extruded of amedical grade polymer sold by Concept Polymer Incorporated under thetrademark C-Flex™. The compression balloon is preferably molded from amedical grade polyester material sold by Allied under the trademarkPET™, that has a limit of stretch based on its initial maximum moldedshape. Alternative materials can include a silicone materialmanufactured by Dow Corning Inc. under the trade name Silastic R™ typeQ7-4850 and type Q7-4765, for the shaft extrusion and the moldedmanifold, and Elastosil type LR3003/30Us for the anchoring balloon 118.The material of catheter 100 preferably has a Shore D hardness between50D and 80D.

After full insertion (i.e., the deflated Foley balloon reaching into thepatient's bladder), a fluid (sterile water) is pumped through the Foleyinflation valve 113 thereby to inflate Foley balloon 118 and hold thecatheter within the patient's urethra. Inflation valve 113 maintainsfluid in the Foley balloon with the desired pressure so that thecatheter is anchored in the patient. However, the catheter is stillcapable of limited longitudinal movement with respect to the urethra.After Foley balloon 118 has been inflated, a warmed fluid, preferably alow-loss liquid (e.g., deionized or sterile water), is slowly pumpedthrough the one or more catheter inflation/circulation lumens 120 (FIG.3 a) into the prostate compression balloon 112 to inflate the sameexpanding the urethral walls and maintaining the temperature of theurethral walls above 30° C. The diameter of the inflated compressionballoon would be approximately in the range of 25-60 French. The warmedfluid used to inflate compression balloon 112 is preferably a minimallyenergy absorptive solution which conducts microwaves to the tissue to beheated more efficiently.

A typical implementation of a catheter according to the invention isshown in FIG. 3. Foley balloon 118 is deflated in this Figure. As shownon the left-hand side of the Figure, a Foley inflation valve 113, awarmed, sterile-fluid intake 115 a and a sterile-fluid outtake 115 b areprovided to receive fluid. The sterile-fluid intake and outtake 115 a,115 b enable the circulation of sterile fluid in the compression balloonduring thermotherapy and maintain the desired pressure to achieve thespecific fluid flow pattern and distribution of fluid within theballoon. A central lumen 126 receives the energy-emitting source 110,which may be an antenna in the form of a coaxial cable. As shown in FIG.3 a, protrusions 127 are formed in central channel 126 in order to keepenergy-emitting source 110 centralized inside catheter 100 and to createchannels for the outtake fluid flow. Protrusions 127 enable the distancebetween the energy-emitting source and outside wall of the catheter toremain constant thereby ensuring a consistent heating pattern at theenergy-emitting portion of the source 110. The energy emitting source110 is directed coupled to the low-loss fluid to maximize emitted powerand to cool the shaft of the energy-emitted source.

As shown in FIG. 4, orifices 122, 124 are employed in one or more ofcatheter lumens 120 on both sides of compression balloon 112 so thatwarmed fluid can be pumped through lumens 120 into compression balloon112 at one end and out at the other end. The warmed water is thencirculated through central orifice 126, which holds an energy-emittingsource 110, such as a microwave antenna, and flows out of catheter 100external of a patient. The placement and diameter of the orifices 122,124 enables sufficient fluid flow and pressure of about 10-25 psi to bemaintained in compression balloon 112 during the entire thermotherapytreatment. In the preferred embodiment, outtake-fluid-side channel isfitted with a restrictive orifice 116 to limit the compression balloonpressure for maximum fluid flow through compression balloon 112. Therestrictive orifice 116, in an alternative embodiment, can be locatedimmediately external to the catheter in the connective tubing (e.g., 115a, 115 b) used to connect the catheter to the external fluid warmingpumping system (FIG. 3 b). The pressurized circulation of the warmedfluid is such that air pockets are reduced in the inflated balloon.Accordingly, air pockets in the compression balloon, which may result in“hot spots” causing burns on the urethral walls, are avoided. Thisresults in the desired compression of the prostatic urethral tissue,without burning the urethral walls, which is maintained during and afterthe thermotherapy treatment.

It is desired to heat the diseased prostate tissue to a therapeutictemperature (greater than about 43° C.) while maintaining thetemperature of the non-prostate tissue lining the urethra above 30° C.The non-prostate tissue includes the urethral wall and adjacent tissueand is disposed between the energy-emitting source 110 and prostatictissue 12. The energy-emitting portion 110 a of source 110 is disposedin catheter 100 so that it rests within the compression balloon 112.Energy-emitting portion 110 a preferably emits an irradiating microwavefield, which varies as an inverse function (e.g., inverse square) of thedistance between the energy-emitting portion 110 a (e.g., microwaveantenna) and the tissue to be heated. Consequently, the non-prostatetissue of urethral wall 10, which is closer to energy-emitting portion110 a than prostatic tissue 12, would be heated to a higher temperaturethan the prostatic tissue to be treated. Likewise, proximate prostatetissue would be heated to a higher temperature than more distal prostatetissue.

U.S. Pat. No. 5,007,437 to Sterzer discloses the use of a balloon tocompress the prostate tissue and to move the urethral wall away from themicrowave antenna, which produces the heat. This method reduced themicrowave field intensity and the resultant heat produced at theurethral wall by moving the urethral wall further from theheat-producing antenna. However, Sterzer also employed a circulatingfluid to continuously cool the urethral wall while the urethral wall wasinflated. Applicants recognized that this circulating coolant waspreventing the urethral wall and adjacent prostatic tissue from reachinga temperature sufficient to denature the protein or enable plasticremodeling. As a result, Applicants theorized that the use of aninflated prostate compression balloon together with the circulation ofwarmed fluid would mitigate the denaturing problem, as shown in FIGS. 5a and 5 b.

FIGS. 5 a and 5 b respectively show a cross-section of a deflatedcompression balloon and a cross-section of an inflated compressionballoon. The radial distances from energy-emitting source or microwaveantenna 110 to distal prostatic tissue 202 and proximal tissue 204,which includes the urethral wall and adjacent non-prostatic tissue, whencompression balloon 112 is deflated are smaller than those distances arewhen compression balloon 112 is inflated. As shown, inflated compressionballoon 112 forms a symmetrical toroid extending around the entirecircumference of the urethral catheter. Specifically, the radialdistance R_(1b) from microwave antenna 110 to the inner circumference ofproximal tissue 204 with inflated compression balloon 112 issignificantly larger than the corresponding radial distance R_(1a) withdeflated compression balloon 112. Similarly, the radius R_(2b) to theinner circumference of prostate tissue 202 with inflated compressionballoon 112 is significantly larger than the corresponding radialdistance R_(2a) with deflated compression balloon 112. Because prostatetissue is soft and compressible, the difference between the outer andinner radii R_(3b) and R_(2b) of prostate tissue 202 with inflatedcompression balloon 112 is substantially reduced with respect to thecorresponding difference between radii R_(3a) and R_(2a) with deflatedcompression balloon 112.

Consequently, the inflated compression balloon causes the prostate 12 tobe compressed from the urethral wall thereby decreasing the thickness ofthe tissue between the compressed wall of the urethra and the margins ofthe prostate capsule. The tissue more distal 202 is not as compressed asthe tissue more proximal to the urethra 204. Since the actual tissuethickness through which the energy emitted by the antenna 110 is less,the energy deposited is more evenly distributed throughout the entireprostate capsule. This makes it possible to heat the prostatic tissuemore evenly and to higher therapeutic temperatures without heating anypart of the non-prostatic tissue beyond its maximum safe temperature.

At the same time the inflated compression balloon 112 constricts theblood flow in the compressed prostate so that the irradiated heat is notcarried away by the natural blood flow and thus makes this tissue moresusceptible to heating by the emitted energy. Since the overall tissuethickness is reduced the amount of energy required to effectively heatthe prostate tissue 204 to a therapeutic temperature is reduced.Conversely, in typical non-compressed therapies, the amount of energyrequired to raise the temperature of the more distal prostatic tissue202, that may be adjacent to the rectal wall to a maximize safetemperature of 41° C. will be significantly higher that than requiredaccording to the invention. Thus, it is possible to heat the prostatictissue more evenly and to higher temperatures without heating any partof the non-prostatic tissue beyond its safe maximum temperature.

In order to heat proximal tissue 204 above a predetermined collagentransition temperature during a microwave thermotherapy treatment,warmed fluid above 30° C., preferably in the range of about 31° C.-60°C., is circulated through compression balloon 112, in contrast to acoolant. As a result, the urethral wall and adjacent tissue issufficiently denatured so that a natural biological stent can be formedafter the thermotherapy treatment.

The warming of the urethral wall above 30° C. and maintaining of thistemperature serves to denature the proteins of the urethral wall; butdoes not heat the urethral wall beyond a maximum safe temperature. Thisdenaturing allows the urethral walls to conform to the expanded shape ofthe urethra created by compression balloon 112 and reduces theelasticity of the urethral walls so that a stent reinforcement periodfollowing the heating of the thermotherapy treatment naturallysolidifies the expanded shape resulting in a biological stent. That is,the expanded urethral walls do not return to their previous shape afterthe compression balloon is deflated and removed thereby achieving anatural opening in the a bodily conduit, such as a urethra.

The stent reinforcement period that follows the termination of theheating of the prostatic tissue requires that the compression balloonremain inflated at the desired pressure of 10-25 psi for less than about10 minutes. During this reinforcement period, fluid typically no longerneeds to be circulated through the compression balloon as only themaintaining of the pressure in the compression balloon serves tosolidify the biological stent. That is, The stent reinforcement periodmaintains the pressure of the compression balloon after power to theenergy-emitting source has been turned off so that a solidified expandedurethra is achieved minutes after thermotherapy and a urine drainagecatheter or other device is not necessary.

Compression balloon 112 is generally cylindrical with a sloped area onboth sides of the compression balloon and is symmetrical along thelength of the diameter according to a preferred embodiment. However,compression balloon 112 may be of any shape to create a desired mold orstent within a bodily conduit or urethra. As shown in FIG. 6, thecompression balloon 112′ on catheter 100 is designed so that it inflatesasymmetrically around catheter 100. The asymmetrical balloon 112′inflates a bodily conduit so that a region of tissue adjacent the bodilyconduit receives more or less radiate energy from the energy-emittingsource 110 depending upon the width of the inflated compression balloon112′. The wider the inflated compression balloon, the more compressedthe tissue adjacent the bodily conduit and the further from the heatproducing source.

Compression balloon 112 needs to maintain about 10-25 psi against theurethral wall along the length of the catheter with the preferred levelof pressure being about 15 psi. The compression balloon may have avariable diameter along the length of the catheter, as shown in FIGS. 7a-7 d. Alternatively, the compression balloon may be a single balloon ormultiple balloons.

In one embodiment, the diameter of the compression balloon varies acrossthe radius to achieve an asymmetric molding of the bodily conduit. Thisshape is shown in FIG. 7 a where the compression balloon only expands toabout 27 French in the middle and 46 F on either end. Alternative shapesof the compression balloon would include cone-shaped cylinders (FIGS. 7b-c) where the apex is adjacent the bladder neck or directed away fromthe bladder neck depending on the desired biological stent. Thesecone-shaped cylinders would enable the energy-emitted to be selectivelyfocused on a particular area surrounding the bodily conduit, as well ascreate a biological stent or opening corresponding to this shape.Alternatively, the cone-shaped or other desired shaped balloons mayprovide preferentially localized therapy for a non-specific disease.

In addition to the various shapes of the compression balloon, thecompression balloon could be covered with a material that shields theenergy-emitting rays so that the heat could be reduced at some portionsof the prostatic tissue and focused at other portions. That is, theshielding would enable preferential heating of prostatic tissue. In thisembodiment, the effective heating area of the catheter/balloon/antennacombination is controlled by a selective addition of distally locatedshielding material provided along the shaft of the catheter eitherinternally or externally applied. Alternatively or in addition to thecatheter shielding material, shielding material may be applied on asurface of the compression balloon, either internally or externally.

The applied shielding when grounded selectively absorbs microwave energyemitted from the energy-emitting source or antenna to modify the heatingpattern and to control the deposition of heat into the surroundingtarget tissue. To electrical ground the shield, internally connectedlead wires are passed through the fluid circulation lumens or embeddedin the catheter shaft material and are connected to the most distal endof the catheter. These wires are then terminated to the externalelectrical surface of the energy-emitting source and/or terminatedseparately to a system grounding point for the adequate dissipation ofthe absorbed emitted energy. The amount and location of shieldingprovided on either the catheter shaft and/or the compression balloon isvariable depending upon the desired heating pattern.

In this embodiment, the energy-emitting source 110 or microwave antennamay be movable so that the position of its energy-emitting portion 110 acan vary to optimize the heating of tissue for a particular therapy. Asshown in FIG. 3 b, a longitudinal antenna locator device 128 would beable to move the antenna and lock the same into the desired position.The preferred location and movement, if any, of the energy-emittingsource would depend on the size, shape and the shielding of thecompression balloon.

Accordingly, the method and apparatus of the present invention ablatethe diseased tissue causing an obstruction in the bodily conduit, whileforming a natural or biological stent in the bodily conduit so edema orswelling does not close the bodily conduit. As a result, an unobstructedopening in a bodily conduit, such as the urethra, is formed after thestent reinforcement period.

Moreover, the circulation of warmed fluid, expansion and heatingaccording to the invention effectively plastically remodels the collagenrich surrounding tissue into a selected shape having a desired expandeddiameter. Thus, the instant invention can increase the patency of theprostatic urethra and surrounding tissue by increasing a urethraldiameter.

More efficient drug delivery may be achieved when used in combinationwith the above-described focused energy and compression thermotherapytreatment. Liposomes are microscopic man-made lipid particles (organiccompounds including the fats, fat-like compounds and the steroids) thatcan be engineered to entrap drugs, creating new pharmaceuticals withenhanced efficacy, better safety or both. In particular, the instantinvention employs heat-sensitive liposomes. Thus, the toxicity ofeffective drugs can be targeted to cancerous tumors or the enlargedprostate due prostatitis through the use of liposome technology.Particular lipids are chosen to make liposomes with liquid-crystal phasetransitions in the range of about 40° to 45° C. where the liposomesundergo abrupt changes in physical properties. Liposomes can have one ormore aqueous compartments that contain the pharmaceutical agent. Theseaqueous compartments are enclosed by a lipid bilayer. While thepreferred temperature for activation of the drug carrier or liposome isapproximately 41° C., lower temperature activation can be realized.

A specific formulation for a heat-sensitive or thermosensitive liposomeis described in U.S. Pat. No. 5,094,854, incorporated herein byreference. Through the use of a higher concentration of liposomes, thanin the prior art, the instant invention should increase the amount ofgeneric or pharmaceutical drug released in the prostate. This increaseddrug per unit area is a result of the higher concentration and thefocused energy employed with the compression of the target area.

Although the present invention has been described with reference topreferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

1. A method of drug delivery to tissue, comprising: inserting into abodily conduit a catheter including an energy-emitting source so thatthe energy-emitting source is positioned adjacent tissue to be treatedand so that focused energy from the energy-emitting source can heat thetissue to be treated, the catheter defining a central lumen and theenergy-emitting source disposed within the central lumen, the catheteralso including a compression balloon; warming a fluid to a temperatureabove approximately 30° C.; inflating the compression balloon with thewarmed fluid to a pressure sufficient to expand the bodily conduit andto compress the tissue to be treated while the energy-emitting source iscontrolled to heat the tissue, the inflating including circulating thewarmed fluid through at least a portion of the catheter into thecompression balloon and then out of the compression balloon into thecentral lumen of the catheter where the energy-emitting source isdisposed; injecting or releasing into the region of tissue to be treateda drug encapsulated within a heat-sensitive liposome; and heating withthe energy-emitting source at least a portion of the tissue to betreated to destroy the heated portion and also to activate theheat-sensitive liposome to release the encapsulated drug such that thedrug targets the tissue to be treated.
 2. The method of claim 1 whereinthe temperature of the circulating warmed fluid is in the range ofapproximately 30° C. to approximately 60° C.
 3. The method of claim 1wherein the heating step comprises heating the at least a portion of thetissue to be treated to a temperature of approximately 43° C.
 4. Themethod of claim 1 wherein the tissue to be treated is the prostate. 5.The method of claim 4 wherein the drug encapsulated within theheat-sensitive liposome treats prostatitis.
 6. The method of claim 1wherein the injecting step comprises injecting the drug encapsulatedwithin the heat-sensitive liposome into the bloodstream of a patient. 7.The method of claim 1 wherein the inflated compression balloon maintainspressure of about 10-25 psi during at least a portion of thethermotherapy.
 8. The method of claim 1 further comprising deflating thecompression balloon and removing the catheter from the bodily conduit.9. The method of claim 8 wherein the temperature of the warmed fluid issufficient to denature proteins of the bodily conduit walls and allowthe bodily conduit walls to conform to the expanded shape of the bodilyconduit created by the inflated compression balloon, such that theexpanded bodily conduit walls do not return to their previous shapeafter the compression balloon is deflated and removed from the bodilyconduit.
 10. The method of claim 8 wherein the expanded bodily conduitwalls remain expanded after the compression balloon is deflated andremoved.
 11. The method of claim 1 wherein the energy-emitting sourcecomprises a microwave antenna.
 12. The method of claim 1 wherein thecompression balloon surrounds the catheter and the energy-emittingsource.
 13. The method of claim 1 further comprising: terminating theheating; maintaining the pressure in the compression balloon afterterminating the heating and for a period of time sufficient to reinforcethe expanded position of the bodily conduit walls; and removing thecatheter from the bodily conduit.